Vorel, J. | bioRxiv Science

bioRxiv2024

Pancreatic cancer cells exchange ribosomes through tunneling nanotubes

O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=112 SRC="FIGDIR/small/597772v3_ufig1.gif" ALT="Figure 1"> View larger version (19K): org.highwire.dtl.DTLVardef@1f66716org.highwire.dtl.DTLVardef@1ea14eeorg.highwire.dtl.DTLVardef@1044da2org.highwire.dtl.DTLVardef@184d8a3_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical abstractC_FLOATNO C_FIG Key pointsO_LIpancreatic tumour cell lines and cells from patient biopsies form tunnelling nanotubes in 2D culture C_LIO_LIformation of tunnelling nanotubes is promoted by gemcitabine C_LIO_LIpolyadenylated mRNAs, ribosomal components and assembled ribosomes are present in tunnelling nanotubes C_LIO_LIribosomes and their components are transferred via nanotubes to acceptor cells C_LIO_LIsilencing of ribosomal proteins S6 and L24 reduces the number of assembled ribosomes C_LIO_LIglobal protein synthesis and number of ribosomes in pancreatic cancer cells with silenced ribosomal proteins increases when co-cultured with translationally unimpaired cells C_LI BackgroundPancreatic ductal adenocarcinoma (PDAC) is considered as one of the deadliest types of cancer. Tunnelling nanotubes (TNTs) are thin, membranous, intercellular communication structures observed in normal and cancer cells, where they mediate the exchange of intracellular material and promote cell fitness, cancer spread and treatment resistance. ResultsPDAC cells increase the formation of TNTs upon exposure to gemcitabine. In the PANC-1 cell line and in tumour explants from patients, we observe polyadenylated mRNA, 5.8S rRNA, ribosomal proteins and assembled 80S ribosomes within the TNTs. Using HaloTag-labelled small ribosomal subunit component RPS9 we demonstrate the transport of ribosomes via TNTs into acceptor cells. Downregulation of ribosomal proteins S6 and L24 decreases the number of assembled ribosomes and the global protein translation in PDAC cells, while a co-culture with translationally unimpaired cells partially restores protein synthesis in cells with impaired protein translation. ConclusionsPDAC cells can exchange components of the protein translation machinery and mRNA. The intercellular transfer of these components causes a partial restoration of protein translation in cells with impaired protein synthesis, which may contribute to the resilience of pancreatic cancer cells, highlighting the potential of targeting TNT dynamics as a therapeutic approach for PDAC.

cancer biology↗

bioRxiv2024

Ergasilid copepods in Africa: first application of next-generation sequencing and update on distribution and phylogenetic position of Ergasilus kandti, a parasite of cichlid fishes

Ergasilidae are a family of globally distributed copepods parasitizing freshwater fish. Despite their widespread occurrence, their phylogeographic patterns are poorly understood, specifically in the African Great Lakes. Here, we aim to provide an update on distribution of Ergasilus kandti, a copepod species infecting Tylochromis polylepis, an endemic cichlid fish species in Lake Tanganyika, and the phylogenetic relationship of African ergasilids. We present the first record of E. kandti parasitizing the gills of T. polylepis in Lake Tanganyika proper, identified through light microcopy and, for the first time for any ergasilid, confocal laser scanning microscopy. We suggest that this technique adds spatial context to characters and are hardly visible while using light microscopy. Phylogenetic analyses based on ribosomal DNA fragments suggest two monophyletic groups of African ergasilids. However, the phylogenetic relationships of Ergasilus remain unresolved, possibly because of the insufficient resolution of these widely used phylogenetic markers and low taxonomic coverage. A comparison of ergasilid mitochondrial genomes highlights traits found in other parasite lineages including genome shrinkage and low evolutionary rates of the cox1 gene. This study presents the most extensive molecular characterization of any ergasilid species to date.

zoology↗